1. Global H5N1 Epidemiology Status of Pandemic Preparedness 29 January 2007 Beijing Keiji Fukuda Global Influenza Programme

2. Overview of Influenza Currently, people affected by 2 forms of influenza –Seasonal human Occurs every year in the world –Avian (H5N1) influenza Primarily infection of birds Occasionally infects people as zoonotic infection Anticipated for future - pandemic influenza –3 in 20 th century –Timing of next uncertain –Could result from H5N1 or another animal influenza virus

3. Spread of Avian H5N1 Influenza Among Birds

4. H5N1 in Poultry or Wildbirds Since 2003

5. H5N1 in Poultry or Wildbirds 1-23 Jan. 2007

6. Since late 2006 Continued disease in poultry in Asia and Africa Asia –China, Indonesia, Japan, Republic of Korea, Thailand & Vietnam Africa –Egypt, Nigeria Infected wild birds in Hong Kong SAR

7. Epidemiology of human H5N1 cases as of 23 Jan 2006 Epidemiology of human H5N1 cases as of 23 Jan 2006

8. WHO Lab-confirmed H5N1 Human Cases As of 28 Jan 2007 YearCases 20034 200446 200597 2006116 20077 Total269

9. WHO Lab-confirmed H5N1 Human Cases As of 28 Jan 2007 CountryCasesDeaths Azerbaijan85 Cambodia66 China2214 Djibouti10 Egypt1911 Indonesia8062 Iraq32 Thailand2517 Turkey124 Viet Nam9342 Total269163

10. Confirmed Human H5N1 Cases 2003 – 28 Jan 2007 Latest maps: http:// gamapserver.who.int/maplibrary/pgrms/avian_influenza.aspxhttp:// gamapserver.who.int/maplibrary/pgrms/avian_influenza.aspx

11. Confirmed Human H5N1 Cases 1- 28 Jan 2007

12. Human H5N1 Cases by Month 2003 – 28 Jan 2007

13. H5N1 Cases by Age Group (N=269)

14. H5N1 Incidence Rates by Age Group Viet Nam & Indonesia Age specific human H5N1 incidence rates in Viet Nam (25 Nov 03 - 24 Nov 06), (n=91) Age specific human H5N1 incidence rates in Indonesia (25 Nov 03 - 24 Nov 06), (n=74) Paper to be published in the WHO Weekly Epidemiological Record on 9 Jan 2007: Update: Epidemiology of WHO-confirmed human cases of avian influenza A (H5N1) infection from 25 November 2003 to 24 November 2006

15. H5N1 Case Characteristics Male / Female : 1.0 (134/135) Illness onset to hospitalisation: Median 4 days (n=201) –2004: 5 days –2005: 4 days –2006: 5 days Illness onset to death : Median 9 days (n=159) –2004: 11 days –2005: 9 days –2006: 9 days

16. H5N1 Case Fatality Case fatality: 61 % (n=269) –2004: 74% (n=46) –2005: 42% (n=104) –2006: 70% (n=109) Sex-specific Case Fatality –Higher in females (67%) than males (54%) [P=0.04] –30 - 39 years: 81% vs 52% [P=0.02).

17. Avian Influenza A/H5N1: Transmission Exposure to poultry –Implicated ~80% of patients –Handling, butchering, plucking feathers, preparing –Ingestion of undercooked poultry (duck blood) Environment –? Contaminated surfaces, water (swimming), fertilizer –? Aerosols of bird droppings; Human to human –Observed associated with conditions of close, intimate contact –Inefficient –No sustained chains of transmission Global –Combinations of movement of poultry, wild birds, other vehicles Ungchusack et al. NEJM 352:333, 2005; Liem et al. Emerg Infect Dis 11:210, 2005

18. Ongoing Evolution of H5N1 Viruses Sub-lineages continue to develop –Gentically & antigenically distinct –Sub-lineages in China Strains isolated from humans –Continue to reflect strains in local poultry populations Confusion over nomenclature –WHO International work group to clarify & standardize

20. Global Challenges and Response

21. Common Challenge for All Countries Scientific & other inherent uncertainties Political sustainability Practicalities Requirements –Time –Strengthening of existing capacities, capabilities & practices –Adoption of new concepts, capacities, practices, attitudes, relationships, technologies –Adequate financial resources

22. Response Needs to Meet the Challenge Acknowledgement of Problem –Global threats differ from local or regional ones Global vision & strategy National capacities Public health oriented tools, relationships & practices Technologies

23. Engagement of Multiple Levels & Programmes At WHO Country & Regional Offices Communications Dangerous Pathogens Ethics Director-General's Office

24. WHO Strategic Action Plan Pandemic Influenza Strengthen Early Warning system Reduce Human Exposure to H5N1 virus Intensify Rapid Containment operations Build Capacity to cope with pandemic Coordinate Global Scientific Research and Vaccine Development 5 4 3 2 1

25. Strengthening Current Capabilities

26. Enhancement of Global Influenza Surveillance Network (GISN) One of the oldest WHO surveillance networks (estab. 1952) Current Network: –Contributing local laboratories, hospitals –116 National Influenza Centres in 87 countries –4 WHO CC on Reference and Research on Influenza –1 WHOCC on Influenza Ecology in Animals –Coordinated by Global Influenza Programme Central, essential role in defence against influenza –For biannual selection of influenza vaccine strains –For global alert for viruses posing pandemic threat

27. Global Influenza Surveillance Network Ongoing Functions & New Developments Additional critical activities –Updated protocols for laboratory methods –Production and provision of WHO diagnostic reagents –Training for laboratory scientists & technicians worldwide –Global pool of experts responding to urgent situations –Testing of viruses for antiviral resistance Enhancements underway –Creation of complementary H5 Reference Network –Increase in Collaborating Centres –Newer approaches to handling of information

28. Examples of New Public Health Tools New International Health Regulations

29. EIDs continue to threaten mankind.. …and place sudden intense demands on national and international health systems ….on some occasions have brought systems to the point of collapse > 1100 events followed by WHO between January 2001 and May 2006

30. … toward a Global Legal Framework, 1995 - 2005 WHA 1995 Creation of EMC 1995 WHA 2001 Global Health Security GOARN 2000 WHA 2005 Adoption of IHR(2005) WHA 2005 Adoption of IHR(2005) Outbreak Verification List 1997 IHR Inter- governmental Working Group2004-05 WHA 2006 Immediate voluntary implementation WHA 2006 Immediate voluntary implementation IHR Regional Consultations 2004-05 Ebola Anthrax Smallpox Meningitis SARS Marburg (Angola) Avian Influenza H5N1 International Coordination Group 1996 Yellow fever Nipah Chikungunya Pandemic threat "Bureau des rumeurs" Kikwit, Zaïre GPHIN 1997-98 Plague BSE XDR-TB EMS 2002

31. The International Health Regulations Public health concept & tool –To improve the identification & rapid reporting of globally important disease threats Existing IHR revised at member state's request Legally-binding global agreement –Adopted at 2005 World Health Assembly –Binding on WHO’s Member States & WHO Full entry into force in June 2007 –Voluntarily adopted in 2006 for pandemic influenza –Implementation of infrastructure, procedures, education underway

32. Example of New Strategies Global Pandemic Influenza Vaccine Action Plan

33. Why a Global Plan? In order to strengthen pandemic-influenza preparedness and response Anticipated gap between vaccine demand and supply during an influenza pandemic Request from WHA 58.5 to WHO secretariat to –seek solutions with international and national partners, including the private sector, –to reduce the potential global shortage of influenza vaccines for both epidemics and pandemics …..

34. Essential Partnerships Governments Research community Foundations Pharmaceutical industry WHO

35. Major Approaches I.Increase use of seasonal influenza vaccine II.Increase production capacity for pandemic vaccines, independent of seasonal vaccine use III.Research and develop new technologies

36. Activities Underway Mapping demand and supply of influenza vaccines Consortium to improve H5N1 vaccines production yields Review of technologies amenable to transfer to developing country manufacturers Establishment of new capacity in developing countries Development of adjuvanted vaccines, whole virus vaccines, intradermal administration etc

37. Example of New Practices Adoption of Executive Board Resolution 26 January 2007 "Avian and pandemic influenza: developments, response and follow up, applications of the International Health Regulations (2005) and best practices for sharing influenza viruses and sequence data"

38. Issues and Context Modern emerging infectious disease threats cannot be handled by any single country –Protection requires effective action by others Mutual global health security is the unifying concept Key information essential for –Disease risk assessment & monitoring –Mobilizing adequate response –Diagnostics, Vaccines, antivirals –Clinical education ….

39. Issues and Context But very real balancing concerns –Inappropriate release & use of information –National sovereignty –Balancing urgent public health response & research practices –Inequity One way flow of information & viruses from affected – often under resourced countries – is not acceptable

40. EB Resolution 120/R.7 Adopted by WHO Executive Board on 26 January 2007 –34 countries Addresses –Support global influenza surveillance –Establishment of mechanisms to ensure routine and timely sharing of biological materials related to novel influenza viruses ….. From both humans and animals ……… and routine placement of data on genetic sequences in publicly available data bases –Support WHO global pandemic influenza vaccine action plan

41. EB Resolution Addresses –Promotion of access to practical products, including pandemic influenza vaccines, resulting from research on influenza viruses …. –Appropriate action if WHO is notified by a Member State that the viruses provided by that Member States were misused for research or commercial purposes in a manner that violates best practice –Facilitation of broader and more equitable regional distribution of the production capacity for influenza vaccine …………

42. EB Resolution Addresses –Support to developing countries, including those sharing their viruses, for building capacity for surveillance, case-detection and reporting ……… –Cooperation with Member States to establish feasible and sustainable incentives ……… for sharing their viruses and genetic sequence information –Mobilization of additional support for Member States with vulnerable health systems …..

43. EB Resolution Addresses –Identification, recommendations and support for the appropriate implementation of possible options aimed at promoting the accessibility of pandemic-influenza vaccine and antiviral medicines to all, for example by …………….

44. Conclusions Balancing complementary generic approaches needed for all disease threats with disease specific actions Use of reality of new global emerging infectious diseases to forge the new practices, relationships needed Strengthen what exists while moving in new directions Accepting ethical dimensions as a practical consideration